Anaemia in pregnancy and infant mortality in Tanzania

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1 Tropical Medicine and International Health volume 9 no 2 pp february 2004 Anaemia in pregnancy and infant mortality in Tanzania Tanya Marchant 1,2, Joanna Armstrong Schellenberg 1,2, Rose Nathan 1, Salim Abdulla 1, Oscar Mukasa 1, Hassan Mshinda 1 and Christian Lengeler 2 1 Ifakara Health Research and Development Centre, Ifakara, Tanzania 2 Swiss Tropical Institute, Basel, Switzerland Summary Tanzania is an area of moderate to high risk for severe anaemia during pregnancy. There is extensive literature examining the consequences of severe anaemia for pregnant women, but the impact this problem has on their infants in malaria-endemic regions is poorly understood. Between 1999 and 2001 we used a demographic surveillance system in the Kilombero Valley, Tanzania to link morbidity and socio-economic status data for 301 pregnant women to the survival of 365 days of their singleton babies, looking for evidence of an association between infant mortality and maternal haemoglobin (Hb). The hazards ratio for infant mortality amongst women who had been severely anaemic in pregnancy (Hb < 8 g/dl) was 3.1 [95% confidence interval (CI) , P ¼ 0.04] compared with women with Hb above this level after controlling for other factors. Prevention of anaemia in pregnancy may lead to an improvement in infant survival. keywords anaemia, infant mortality, pregnancy, interventions, Tanzania, Africa Introduction Women in developing countries account for 95% of anaemic pregnancies in the world. The contribution anaemia makes to maternal morbidity and mortality and its association with low birth weight in sub-saharan Africa is well documented (Shulman 1999a; Guyatt & Snow 2001). In contrast, the impact of maternal anaemia on infant mortality in a developing country context is inconclusive (Xiong et al. 2000) and reviews of the topic highlight the need for more research (Allen 2000; Scholl & Reilly 2000; Xiong et al. 2000). In particular there is a lack of data from settings where the burden of anaemia is high and a large number of women reach term with severe anaemia. An inherent difficulty in prospectively establishing the contribution of anaemia in pregnancy to subsequent infant mortality lies in the ethical necessity for medical intervention. Using a demographic surveillance system (DSS), we investigated the infant mortality of a cohort of babies in southern Tanzania who were born to women for whom detailed morbidity and socio-economic data was collected during pregnancy, including haemoglobin. Materials and methods This research was one component of an anaemia in pregnancy study, which has been described elsewhere (Marchant et al. 2002a). In short, 507 pregnant women were recruited cross-sectionally in the rural Kilombero Valley of Tanzania where there is intense perennial malaria transmission. We used a DSS (Armstrong Schellenberg et al. 2002) to identify and enrol (with consent) all pregnant women in the study area during the study period (September 1998 August 1999). Haemoglobin levels of the pregnant women were collected using a portable b-haemoglobin photometer (Hemocue Ó, HemoCue AB, Ängelholm, Sweden) along with other morbidity and socio-economic data. We then analysed the infant mortality of the babies born to the 507 pregnant women recruited. In total, 301 of the women had live singleton births, which were registered with the DSS, and nine had twins. The birth outcome for 197 of the women was unknown; this was likely to be due to out-migration. We could only follow-up infants who were registered as residents of the DSS. Therefore, data for infants born to women who moved away before or shortly after delivery was lost. The nine sets of twins were discounted from the analysis as we thought that they were at a higher mortality risk than their singleton counterparts. The morbidity and socio-economic characteristics of the mothers of the 301 babies were similar to those of the 206 mothers with twin births or whose birth outcome was unknown. The two differences identified between the two groups were: first, mothers of babies included in the infant mortality analysis were older than those whose 262 ª 2004 Blackwell Publishing Ltd

2 Table 1 Univariate analysis of maternal socio-economic and morbidity data during pregnancy and subsequent infant death Births* Deaths Rate ratio (RR) P-value Age Parity Multigravidae Primigravidae Education Primary None Marital status Ever married Never married Access to cash No Yes Mid-upper arm circumference < Body mass index < Use of ITN No Yes Use of iron No Yes Preterm birth No Yes Severe anaemia No Yes Malaria No Yes Iron deficient No Yes Hookworm No Yes HIV No Yes 0 20 * N ¼ 301 except for the following: hookworm n ¼ 281; iron deficient n ¼ 281; preterm birth n ¼ 300; human immunodeficiency virus (HIV) n ¼ 293; body mass index (BMI), mid-upper arm circumference (MUAC), insecticide treated 3 net (ITN) use n ¼ 299. Mantel Haenszel estimate of the rate ratio. babies were lost to follow-up [mean age 27 years (95% CI 26 28) vs. 24 years (95% CI 23 25): t-test P-value <0.001). Secondly, mothers in the survival analysis had a higher mean gestational age at recruitment to the crosssectional study [31 weeks (95% CI 31 32) vs. 29 weeks (95% CI 28 30): t-test P-value <0.001). No other differences were found. We looked for evidence of an association between infant survival to 365 days and all available maternal morbidity and socio-economic variables collected during pregnancy (Table 1). Variables associated with child survival (log rank test or Mantel Haenszel estimate of the rate ratio, P-value <0.10) were further analysed using Cox proportional hazards regression. Confounding was assessed for each potential confounder in turn through comparison of adjusted and non-adjusted estimates of the Cox hazard ratio (HR): if these varied by more than 10%, the variable was regarded as a confounder. The assumption of proportional hazards was tested using Schoenfeld residuals. Model fit was assessed using Cox-Snell residuals. Results Of the 301 singleton infants traced 22 died within the first year of life. The infant mortality rate for the cohort was Table 2 Assessing confounding for the impact of anaemia on infant death Hazard ratio (HR) 95% confidence interval Unadjusted severe anaemia HR Severe anaemia HR adjusted for Age 3.0* Parity 3.0* Education 4.0* Marital status 3.2* Access to cash Use of ITN Use of iron prophylaxis Malaria Iron status Hookworm HIV status MUAC 3.3* BMI 3.2* Preterm birth Season of birth Gestation in cross-sectional 4.0* Season in cross-sectional 4.6* * Variables which change the HR for severe anaemia by 10%. Cox hazard ratio (HR). HIV, human immunodeficiency virus; BMI, body mass index; MUAC, mid-upper arm circumference. ª 2004 Blackwell Publishing Ltd 263

3 Table 3 Infant mortality rates per 1000 child-years at risk and hazard ratios for infant death by selected maternal variables, Ifakara Births (N) Deaths (N) Childyears at risk Infant mortality rate 95% confidence interval (CI) Unadjusted hazard ratio 95% CI Adjusted hazard ratio*, 95% CI LRT v 2 P-value All Age (years) Marital status Ever married Never married Gravidity Multigravidae Primigravidae Education Primary None MUAC < Body mass index < Hb <8 g/dl No Yes * Model also adjusts for season of recruitment of the pregnant woman (LRT v 2 0.2, P ¼ 0.8) and gestational month at recruitment (LRT v 2 1.2, P ¼ 0.9). Assumption of proportional hazards for final model: v 2 ¼ 10.7, P ¼ /1000 child-years (95% CI ). There was evidence of an association between infant mortality and severe maternal anaemia (Hb < 8 g/dl), maternal age, gravidity and marital status. The season and gestation at which the pregnant woman was recruited, her education status, and her mid-upper arm circumference (MUAC) and body mass index (BMI) scores were identified as potential confounders for the relationship between severe anaemia and death (Table 2) and were also included in the multivariate model. Infant mortality rates and unadjusted and adjusted HR for these variables are shown in Table 3. Severe anaemia was associated with a threefold increase in the HR for infant mortality after adjustment for age, gravidity, marital status, education, MUAC and BMI scores and gestation and season (HR 3.1, 95% CI , 1 likelihood-ratio test (LRT), P ¼ 0.04). None of the other variables included in the model were significant after adjustment. The Kaplan Meier survivor functions, adjusted for maternal age, for children born to anaemic and non-anaemic women are shown in the Figure 1. Survivor functions are higher at all time points throughout the first year of life for infants born to women not severely anaemic compared with those with Hb < 8 g/dl. Discussion After controlling for other factors the mortality rate of infants born to women with severe anaemia in pregnancy was three times that of infants born to women who did not have severe anaemia in rural Tanzania. The health consequences to the mother of anaemia at the time of delivery may be compounded by the adverse effects of maternal anaemia on the young foetus, manifested by an increased infant mortality rate. 264 ª 2004 Blackwell Publishing Ltd

4 Days An inherent limitation of our cross-sectional data on health in pregnancy is that previous history and subsequent events are unknown. Women found not to be anaemic in the cross-sectional study may have become so later in pregnancy. However, as 209 of 301 (70%) of participants were already in the third trimester, this is unlikely to have affected the results. Severe anaemia was found in 55 of 507 (11%) of the pregnant population (Marchant et al. 2002a) around Ifakara, an environment which is typical of other East African regions of moderate to high risk for severe anaemia in pregnancy. It is a poor, rural area where there is food insecurity and delivery systems for health interventions are weak. The aetiology of severe anaemia was multifactorial with malaria, hookworm and iron deficiency contributing. Socio-economic factors also played a role most likely via food insecurity. In this setting, women commonly enter pregnancy with depleted iron stores and progress to more severe degrees of anaemia. The severely anaemic women in this study represent women who had been anaemic for some time as well as new cases. Preventive interventions to tackle the principal risk factors for maternal anaemia in East Africa, malaria (Guyatt & Snow 2001) and iron deficiency (Allen 2000), are available in principle. Insecticide-treated nets have been associated with a protective efficacy of 38% (95% CI 4 60) for severe anaemia in pregnancy (Marchant et al. 2002b) and the commitment to increase coverage is ongoing both at local and national level in Tanzania. Intermittent presumptive treatment in pregnancy with sulphadoxine-pyrimethamine has been associated with a protective efficacy of 39% (95% CI 22 52) for severe anaemia (Shulman et al. 1999b), and is now part of the national malaria control policy for Tanzania. Iron supplementation in pregnancy can improve haemoglobin levels No Yes Figure 1 Kaplan Meier survival functions for infants to 365 days, according to presence or absence of maternal severe anaemia (Hb < 8 g/dl) during pregnancy. even in settings of multiple aetiologies for anaemia, including malaria (Mahomed 2001), although it has been observed that improvements in the haemoglobin of severely anaemic women with iron supplementation alone are less impressive than for women with an initial Hb > 10 g/dl (Vitteri 1998). Multiple aetiologies require multiple interventions, as is already the policy for the prevention of anaemia in pregnancy in Tanzania. The two most pressing challenges now are to strengthen the distribution systems for these interventions and to promote a more timely use of antenatal services. In conclusion, our finding of a threefold increase in infant mortality for babies born to women with severe anaemia in pregnancy reinforces anaemia in pregnancy as a priority area of concern. Improving access to interventions tackling this problem may help to improve child survival as well as reducing maternal morbidity and mortality. Acknowledgements The authors thank the women who participated in the study, all staff of Ifakara Health Research and Development Centre, Dr P. Mbena (District Medical Officer) and the MCH clinic staff. Authors are grateful also to Prof. M. Tanner and to Dr D. Schellenberg. Ethical clearance was obtained from the Ifakara Health Research and Development Centre and the Tanzanian Commission of Science and Technology. Financial support was provided by the Swiss Agency for Development and Co-operation and the Government of Tanzania. T. Marchant was partly supported by a fellowship from the Rudolf Geigy Foundation. References Allen LH (2000) Anaemia and iron deficiency: effects on pregnancy outcome. American Journal of Clinical Nutrition 71, S1280 S1284. Armstrong Schellenberg JRM, Mukasa O, Abdulla S et al. (2002) The Ifakara Demographic Surveillance System. In: INDEPTH Monograph Series: Demographic Surveillance Systems for Assessing Populations and their Health in Developing Countries, Vol. 1: Population, Health and Survival in INDEPTH Sites. IDRC/CRDI, Ottawa, pp Guyatt HL & Snow RW (2001) The epidemiology and burden of Plasmodium falciparum-related anaemia among pregnant women in sub-saharan Africa. American Journal of Tropical Medicine and Hygiene 64, Mahomed K (2001) Iron supplementation in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 1, Update 2 Software, Oxford. John Wiley & Sons Ltd, Chichester, UK. Marchant T, Armstrong Schellenberg JRM, Edgar T et al. (2002a) Anaemia in pregnancy in southern Tanzania. Annals of Tropical Medicine and Parasitology 96, ª 2004 Blackwell Publishing Ltd 265

5 Marchant T, Armstrong Schellenberg JRM, Edgar T et al. (2002b) Socially-marketed insecticide-treated nets improve malaria and anaemia in pregnancy in southern Tanzania. Tropical Medicine and International Health 7, Scholl TO & Reilly T (2000) Anaemia, iron and pregnancy outcome. Journal of Nutrition 130, S443 S447. Shulman CE (1999a) Malaria in pregnancy: its relevance to safe-motherhood programmes. Annals of Tropical Medicine and Parasitology 93, S59 S66. Shulman CE, Dorman EK, Cutts F et al. (1999b) Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomized placebo controlled trial. Lancet 353, Vitteri FE (1998) Iron supplementation for the control of iron deficiency in populations at risk. Nutritional Reviews 55, Xiong X, Buekens P, Alexander S et al. (2000) Anaemia during pregnancy and birth outcome: a meta-analysis. American Journal of Perinatology 17, Authors 4 Tanya Marchant (corresponding author), JMP, PO Box 2228, KCMC, Moshi, Tanzania. tanyamarchant@hotmail.com Joanna Armstrong Schellenberg, Rose Nathan, Salim Abdulla, Oscar Mukasa and Hassan Mshinda, Ifakara Health Research and Development Centre, PO Box 53, Ifakara, Tanzania. dajobelo.com@aol.com, rnathan@ifakara.mimcom.net, sabdulla@ifakara.mimcom.net, omukasa@ifakara.mimcom.net, hmshinda@ifakara.mimcom.net Christian Lengeler, Swiss Tropical Institute, Socinstrasse 57, 4002 Basel, Switzerland. christian.lengeler@unibas.ch 266 ª 2004 Blackwell Publishing Ltd